The time that blood spends in the pulmonary capillaries is a major determinant of gas exchange effectiveness of the lung. Consequently, physiologic mechanisms which alter this contact time may serve important regulatory functions. For example, during exercise, some factors reduce contact time so that more red blood cells traverse the capillaries per unit time, thereby enhancing gas exchange. Furthermore, it is clear that exceedingly rapid transit can cause arterial hypoxemia. Despite the obvious importance of understanding microcirculatory hemodynamics in the lung, previous investigators have been forced to use indirect techniques and, in terms of red blood cell capillary transit itme, to consider the lung as a single, homogeneous entity. In fact, it is likely that regional differences in pressure and flow within the lung give rise to regional differences in capillary transit. Using in vivo videomicroscopy techniques recently developed in this laboratory, we propose to determine directly the length of time required for red blood cells to traverse pulmonary capillaries and to evaluate how transit time changes as a function of the hydrostatic gradient along the vertical dimension of the lung. We will also investigate the physiologic variables (pulmonary arterial and venous pressures, cardiac output, and pulmonary capillary recruitment) that influence regional capillary transit times. Specific emphasis is placed on mechanisms that reduce transit time in order to increase gas exchange and limit transit time to defend against hypoxemia. Finally, we will determine whether sympathetic nerve stimulation alters capillary transit time, thereby providing evidence for a physiologic role of neural elements in regulating the capillary transit time in the lung.